AstroCapsules offer a new way to reduce brain inflammation

Neuroinflammation is linked to a host of detrimental brain disorders, including Alzheimer's and Parkinson's disease. A collaborative research team from Houston Methodist and Rice University has developed a way to fight back with a tiny, bioengineered system to deliver anti-inflammatory proteins to specific targets in the brain.

The study, recently published in Biomaterials, was led by Robert Krencik, an associate professor in the Center for Neuroregeneration and Department of Neurosurgery at the Houston Methodist Research Institute. The paper reveals the creation of AstroCapsules, a revolutionary union of bioengineering and neuroscience that encloses human astrocytes (star-shaped, resident brain cells that are crucial to healthy function of the central nervous system) within small biocompatible hydrogel capsules.

The researchers found that when astrocytes within the capsules were armed with a secreted anti-inflammatory protein (interleukin-1 receptor antagonist or IL-1Ra), they could significantly reduce neuroinflammation (measured through inflammatory biomarkers). Importantly, the AstroCapsules (which are 300 micrometers in diameter-approximately the size of large grains of sand) were confirmed to function when implanted into the brain, showing they could withstand rejection from the body's immune system. The researchers conducted their research using lab-grown human brain tissue samples, known as organoids, and by using mouse models.

This system solves several current problems with cell-based therapeutics to the nervous system. Because the capsules will form a physical barrier between the implanted astrocytes and brain tissue, cells are expected to locally secrete anti-inflammatory proteins while avoiding immune rejection and unwanted migration throughout the brain. This will increase stability of the treatment while reducing side effects."

Robert Krencik, associate professor, Center for Neuroregeneration and Department of Neurosurgery, Houston Methodist Research Institute

The researchers said this represents a new way to treat devastating neurodegenerative diseases and showcases how cell therapy can actively diminish damaging inflammation in the brain.

"Encapsulating cells in a way that shields them from immune attack has been a central challenge in the field," said the co-corresponding author on the study, Omid Veiseh, a professor of bioengineering at Rice. "In our lab, we have been working on biomaterials for many years, and this project was an opportunity to draw from that experience to address the uniquely complex immune environment of the brain. Our hope is that this work will help move cell therapies closer to becoming real treatment options for patients with neurodegenerative disease." 

The study was coauthored by Samira Aghlara-Fotovat, Maria Montalvo-Parra, Sajedeh Nasr Esfahani,
Katherine E. Rosner, Suki Oji, Samantha Fleury, Megh Patel, Aboud Tahanis and Caroline Cvetkovic. Aghlara-Fotovat, Montalvo-Parra and Nasr Esfahani contributed equally to the research.